https://scholars.lib.ntu.edu.tw/handle/123456789/465734
標題: | A theranostic micelleplex co-delivering SN-38 and VEGF siRNA for colorectal cancer therapy | 作者: | Lee, Shin-Yu Yang, Chia-Ying Peng, Cheng-Liang Wei, Ming-Feng KE-CHENG CHEN Yao, Cheng-Jung MING-JIUM SHIEH |
關鍵字: | Colorectal cancer; Micelleplex; Micelles; MRI; SN-38; VEGF siRNA | 公開日期: | 2016 | 出版社: | Elsevier Ltd | 卷: | 86 | 起(迄)頁: | 92-105 | 來源出版物: | Biomaterials | 摘要: | The development of an efficient colorectal cancer therapy is currently a public health priority. In the present work, we proposed a multifunctional theranostic micellar drug delivery system utilizing cationic PDMA-block-poly(ε-caprolactone) (PDMA-b-PCL) micelles as nanocarriers of SN-38 (7-ethyl-10-hydroxycamptothecin), ultra-small superparamagnetic iron oxide nanoparticles (USPIO), and small interfering RNA (siRNA) that targets human vascular endothelial growth factor (VEGF). The VEGF siRNA was conjugated to polyethylene glycol (PEG) (siRNA-PEG) before complexation with the micelles in order to improve the siRNA's stability and to prolong its retention time in the blood circulation. To further improve the in vivo biosafety, we prepared mixed micelles using mPEG-PCL together with PDMA-b-PCL copolymer. The SN-38/USPIO-loaded siRNA-PEG mixed micelleplexes passively targeted to tumor regions and synergistically facilitated VEGF silencing and chemotherapy, thus efficiently suppressing tumor growth via a multi-dose therapy regimen. Additionally, the SN-38/USPIO-loaded siRNA-PEG mixed micelleplexes acted as a negative magnetic resonance imaging (MRI) contrast agent in T2-weighted imaging, resulting in a powerful tool for the diagnosis and for tracking of the therapeutic outcomes. In summary, we established a theranostic micellar drug and gene delivery system that not only synergistically combined gene silencing and chemotherapy but also served as a negative MRI contrast agent, which reveal its potential as a novel colorectal cancer therapy. © 2016 Elsevier Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84975684134&doi=10.1016%2fj.biomaterials.2016.01.068&partnerID=40&md5=40e1b99f751a4b9e08198ee58a041731 https://scholars.lib.ntu.edu.tw/handle/123456789/465734 |
ISSN: | 0142-9612 | DOI: | 10.1016/j.biomaterials.2016.01.068 |
顯示於: | 醫學工程學研究所 |
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